2QO8

Crystal structure of the complex of hcaii with an indane-sulfonamide inhibitor

2QO8 の概要

• エントリーDOI: 10.2210/pdb2qo8/pdb
• 関連するPDBエントリー: 1CA2 2QOA 2QP6
• 分子名称: Carbonic anhydrase 2, ZINC ION, MERCURIBENZOIC ACID, ... (6 entities in total)
• 機能のキーワード: carbonic anhydrase ii, lyase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P00918
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 30067.63

構造登録者

D'Ambrosio, K.,De Simone, G. (登録日: 2007-07-20, 公開日: 2008-01-22, 最終更新日: 2023-08-30)

主引用文献

D'Ambrosio, K.,Masereel, B.,Thiry, A.,Scozzafava, A.,Supuran, C.T.,De Simone, G.
Carbonic Anhydrase Inhibitors: Binding of Indanesulfonamides to the Human Isoform II.
Chemmedchem, 3:473-477, 2007

PubMed Abstract: Indanesulfonamides are interesting lead compounds for designing selective inhibitors of the different isoforms of the zinc enzyme Carbonic Anhydrase (CA). Herein, we report for the first time the X-ray crystal structure of two such derivatives, namely indane-5-sulfonamide and indane-2-valproylamido-5-sulfonamide, in complex with the physiologically dominant human isoform II. The structural analysis reveals that, although these two inhibitors have quite similar chemical structures, the arrangement of their indane ring within the enzyme active site is significantly diverse. Thus, our findings suggest that the introduction of bulky substituents on the indane-sulfonamide ring may alter the binding mode of this potent class of CA inhibitors, although retaining good inhibitory properties. Accordingly, the introduction of bulky tail moieties on the indane-sulfonamide scaffold may represent a powerful strategy to induce a desired physicochemical property to an aromatic sulfonamide or to obtain inhibitors with diverse inhibition profiles and selectivity for various mammalian CAs.

PubMed: 18161740
DOI: 10.1002/cmdc.200700274

実験手法

X-RAY DIFFRACTION (1.4 Å)